Local Anesthetics

Question 1

What are local anesthetic used for?

Answer 1

they are used to reversibly block nerve conduction in a particular region of the body

Question 2

What are all LA’s analogs of?

Answer 2

cocaine

Question 3

What are the methods of local anesthetic administration (5)?

Answer 3

topical administration, infiltration, nerve block, spinal block, epidural block

Question 4

What’s unique about cocaine (4)?

Answer 4

administered topically, goes through mucosal membranes, used for EENT, causes vasoconstriction

Question 5

In what form can LA’s penetrate membranes?

Answer 5

in the unionized form

Question 6

What sort of analgesia can spinal block produce?

Answer 6

regional (as well as local)

Question 7

What are the thee parts that make up the structure of LA’s?

Answer 7

ionizable “head”, an amide or ester containing connecting chain, and a non-polar “tail” usually containing a phenyl ring.

Question 8

Are clinically used LA’s acidic or basic?

Answer 8

weak bases usually containing a tertiary amino group as hydrophilic, cationic group

Question 9

What are the ester type drugs (4)?

Answer 9

cocaine, procaine, benzocaine, tetracaine

Question 10

What are the amine type drugs (3)?

Answer 10

lidocaine, Mepivacaine (R=methyl), Bupivacaine (R=butyl)

Question 11

What’s unique about benzocaine?

Answer 11

low water solubility and less polar, so can’t be injected and is instead used topically (often an ingredient in after sun lotions)

Question 12

Which type have a greater vasodilatory effect?

Answer 12

I think he said ester type…? but of course not cocaine

Question 13

What’s unique about Tetracaine?

Answer 13

very lipophilic, one of the most potent, long duration of action. limited to spinal injection

Question 14

What’s unique about bupivacaine?

Answer 14

spinal injection, lipphilic, long-acting, potent, CARDIOTOXIC

Question 15

What’s unique about mepivacaine?

Answer 15

advantage over lidocaine = less adverse effects

Question 16

What’s special about Lidocaine?

Answer 16

prototype of amide types

Question 17

What’s special about procaine?

Answer 17

=Novacane, large vasodilatory effect

Question 18

How do LA’s work?

Answer 18

they preferentially block voltage-dependent sodium channels in nerve and muscle membranes. “lipid route” on extracellular fluid side, “polar” route on intracellular fluid side

Question 19

What is the relationship between intensity of local anesthesia and spike frequency? Why?

Answer 19

intensity increases with spike frequency because the opened and inactivated states of the sodium channel, which bind the LA most readily, are occupied a greater fraction of the time,

Question 20

upon which cells are LA’s most effective?

Answer 20

active cells.

Question 21

Which is more lipophilic- bupivacaine or lidocaine?

Answer 21

bupivacaine

Question 22

Why does bupivacaine modify the normal cardiac rhythm?

Answer 22

block by bupivacaine occurs in the normal frequency range of the myocardium.

Question 23

What does Lidocaine selectively block and why?

Answer 23

tachycardias, because it only displays its maximal blocking activity at much higher than normal beat frequencies.

Question 24

What is the major toxicity of bupivacaine? why?

Answer 24

cardiotoxicity due to its slow rate of dissociation from the myocardial sodium channel

Question 25

Which form most rapidly penetrates the sheath and plasma membranes?

Answer 25

the unionized form

Question 26

Which form is most active in blocking the sodium channel?

Answer 26

the cationic amine form

Question 27

Since bupivacaine and lidocaine both have frequency-dependent block of sodium channels, what can they be used for?

Answer 27

antiepileptic in brain and antiarrhythmic in heart

Question 28

What is one major problem with LA’s and what accentuates is?

Answer 28

Vascular absorption- this problem is accentuated by the vasodilatory actions of all LAs except for cocaine.

Question 29

What can be added to slow vascular absorption? what does this do?

Answer 29

vasoconstrictors like epinephrine. this increased the rate and intensity of nerve block and prolongs the duration of action.

Question 30

What does reduced plasma LA concentration mean? what’s up with newer LAs?

Answer 30

fewer systemic complications. newer LAs produce less vasodilation

Question 31

What can happen when LAs are incorrectly injected or absorbed too rapidly?

Answer 31

systemic toxicity! CNS convulsion and depression (leading to respiratory depression) may occur.

Question 32

What are the pharmacological antagonists for systemic toxicity?

Answer 32

there are none! treatment includes artificial respiration with pure oxygen and administration of anticonvulsant (Valium)

Question 33

What is the relationship between Lidocaine plasma concentration and its pharmacological effects?

Answer 33

anti-arrhythmic at very low doses…circumoral and tongue numbness…lightheadedness, tinnitus…visual disturbances…muscular twitching…convulsions…coma…respiratory arrest…cardiovascular depression

Question 34

How are ester LAs metabolized?

Answer 34

they are hydrolyzed by plasma (non-specific) cholinesterase

Question 35

How are amide LAs metabolized?

Answer 35

they are dealkylared and hydrolyzed in the liver

Question 36

What is the major factor in determining the duration of local anesthesia?

Answer 36

vascular absorption

Question 37

Why is metabolism important (2)?

Answer 37

Controlling a) the antiarrhythmic duration of action of procainamide and lidocaine and b) fetal CNS depression due to absorption of LA from mommy’s circulation